Brand  (β version)

PDB ID: 6EDS

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Ligands
Code Name Style Show Link
J22 {(8r,9s,10s)-9-(2',3'-dimethyl[1,1'-biphenyl]-4-yl)-6-[(1-methyl-1h-imidazol-2-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]decan-10-yl}methanol PoSSuM
EPE 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid PoSSuM
PEG Di(hydroxyethyl)ether PoSSuM
DIO 1,4-diethylene dioxide PoSSuM
Non-standard Residues
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Structure summary

Code : 6EDS   PDBj   RCSB PDB   PDBe
Header : HYDROLASE/INHIBITOR
Title : Structure of Cysteine-free Human Insulin-Degrading Enzyme in complex with Glucagon and Substrate-selective Macrocyclic Inhibitor 63
Release Data : 2019-04-03
Compound :
mol_id molecule chains synonym
1 Insulin-degrading enzyme A,B Abeta-degrading protease,Insulin protease,Insulinase,Insulysin
ec: 3.4.24.56
mutation: C110L, E111Q, C171S, C178A, C257V, C414L, C573N, C590S, C789S, C812A, C819A, C904S, C966N, C974A
mol_id molecule chains
2 Glucagon C,D
other_details: Glucagon, marketed as Glucagen and manufactured by Boehringer Ingelheim.
Source :
mol_id organism_scientific organism_common expression_system
1 Homo sapiens  (taxid:9606) Human Escherichia coli BL21(DE3)  (taxid:469008)
gene: IDE
expression_system_strain: BL21(DE3)
mol_id organism_scientific organism_common expression_system
2 Homo sapiens  (taxid:9606) Human Saccharomyces cerevisiae  (taxid:4932)
gene: GCG
Authors : Tan, G.A., Seeliger, M.A., Maianti, J.P., Liu, D.R., Welsh, A.J.
Keywords : Insulin, Glucagon, Diabetes, Exo-site, HYDROLASE, HYDROLASE-INHIBITOR complex
Exp. method : X-RAY DIFFRACTION ( 3.18071730876 Å )
Citation :

Substrate-selective inhibitors that reprogram the activity of insulin-degrading enzyme.

Maianti, J.P.,Tan, G.A.,Vetere, A.  et al.
(2019)  Nat.Chem.Biol.  15 : 565 - 574

PubMed: 31086331
DOI: 10.1038/s41589-019-0271-0

Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones.

Maianti, J.P.,McFedries, A.,Foda, Z.H.  et al.
(2014)  Nature  511 : 94 - 98

PubMed: 24847884
DOI: 10.1038/nature13297

Reaction

Chain : A, B
UniProt : P14735 (IDE_HUMAN)
Reaction: EC: Evidence:
Physiological Direction:
Degradation of insulin, glucagon and other polypeptides. No action on proteins. 3.4.24.56 PubMed:10684867, PubMed:17051221, PubMed:17613531, PubMed:18986166, PubMed:19321446, PubMed:21098034, PubMed:2293021, PubMed:23922390, PubMed:24847884, PubMed:26394692, PubMed:29596046
-
Chain : C, D
UniProt : P01275 (GLUC_HUMAN)
Reaction : -